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Uropathogenic Escherichia coli (UPEC) causes up to 90% of urinary tract infections (UTI) which is more prevalent among females than males. In urine, patients with symptomatic UTI usually have a high concentration of bacterial infection, ≥ 105 colony-forming units (CFU) per mL, in which the culture method is regularly the gold standard diagnosis. In this study, a simple and inexpensive distance-based paper device (dPAD) combined with the fluorescent closed tube LAMP assay was validated for simultaneously screening and semi-quantifying the infection level of E. coli in 440 urine samples of patients with UTI. The dPAD could measure the LAMP amplicons and semi-quantify the levels of E. coli infection in heavy (≥ 104 CFU/mL), light (≤ 103 CFU/mL) and no infection. The sensitivity and specificity had reliable performances, achieving as high as 100 and 92.7%, respectively. The one step LAMP assay could be performed within 3 h, which was 7.5 times faster than the culture method. To empower early UTI diagnosis and fast treatment, this inexpensive dPAD tool combined with the fluorescent closed tube LAMP assay is simple, reliably fast and practically portable for point-of-care settings, particularly in resource-limited areas, which can be set up in all levels of healthcare facilities. [ABSTRACT FROM AUTHOR]

A nanocatalytic antimicrobial gel responsive to the bacterial infection microenvironment (IME) possessing highly specific antimicrobial properties provides an opportunity to address the bacterial drug resistance. However, the pH conditions and low substrate concentration in the IME limit the catalytic antimicrobial efficiency of these agents, resulting in unsatisfactory performance. The reported transition metal peroxide alleviates endogenous substrate insufficiency due to H2O2 self-supplying properties, but still suffers from difficulties of simple synthesis, long-stem storage and lower intrinsic catalytic efficiency responsive to the IME. In this paper, we report for the first time the use of cerium-manganese bimetallic peroxide nanoparticles (CeMnOx) as a nanocatalyst with high pH responsiveness, H2O2 self-supplying properties, multiple ROS-generating activity and synergistic effect-enhanced cascade catalytic reactions for efficient antimicrobial therapy. CeMnOx achieved more than 95% kill rate at 50 mg mL-1 for E. coli and 100 mg mL-1 for S. aureus, which was superior to those of previously reported works. To further improve the availability, nanoparticle-carrying hydrogels with excellent antimicrobial properties were prepared through in situ gelation, thus adapting to a wider range of antimicrobial application scenarios. Therefore, the in situ molded nanocatalytic antimicrobial gels provide a promising paradigm for efficient treatment of bacterial infections. [ABSTRACT FROM AUTHOR]

Background Bacterial culture is the gold standard for the diagnosis of invasive bacterial diseases (IBDs) but molecular methods are more specific and sensitive. Fresh liquid samples (FLSs) show patent limitations for shipping and storage. We aimed to evaluate the sensitivity and specificity of real-time polymerase chain reaction (PCR) performed on dried sample spots (DSSs) obtained from different biological fluids compared with real-time PCR or culture performed on FLSs. Methods FLSs positive for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, Streptococcus pyogenes, Staphylococcus aureus, Bordetella pertussis and/or Pseudomonas aeruginosa were spotted on filter paper. Real-time PCR was performed on both FLSs and DSSs and results were compared. The stability of the DSS results over time was evaluated. Results Real-time PCR performed on 114 DSSs showed a specificity of 99.1% and a sensitivity of 91.2% for IBD diagnosis. A positive correlation was found between FLS cycle threshold (Ct) and DSS Ct (r=0.84; r2=0.71) with the Pearson statistical test and Bland–Altman analysis showing that 95% of the specimens were within agreeable limits. Although we observed a trend towards signal reduction over time in the DSSs, there was no statistical evidence of an increase in Ct values. Real-time PCR on DSSs was 2.2 times more sensitive than culture. Conclusions Real-time PCR applied to DSSs may be a useful approach in different situations, such as IBD diagnosis, both for rural areas of low-income countries and family practitioners in various settings. [ABSTRACT FROM AUTHOR]

Introduction Ashwagandha, a traditional Indian plant, is gaining increasive attention from scientists worldwide due to its potential health benefits, especially in the context of its antibacterial and anticancer properties. Aim of the study The aim of this review was to discuss recent findings regarding the impact of Withania Somnifera on antibacterial effect and its potential applications in anticancer therapy. Materials and methods: The paper was created based on the Pubmed and Google Scholar database. The literature was reviewed using the keywards:,,Ashwagandha”,,,Withania Somnifera”,,,antibacterial ”,,,anticancer”,,,side effects”,,,breats cancer”. Results Studies have confirmed Withania Somnifera, exhibits significant anticacterial and anticancer effects. It inhibits the growth of both Gram-negative and Gram-positive bacteria. Futhermore, it demonstrates anticancer activity, especially in breast cancer, by stimulating apoptosis, induction of cytotoxic effects on cancerous cells and increasing cell sensitivity to radiation. Conclusion Despite promising results, futher research on the benefits of Ashwagandha, particulary in the long term, is essential. There is growing need of more research of the potencial benefits of Ashwagandha in the treatment of various disorders including cancer and bacterial infections and to develop more effective therapeutic strategies. The need for large randomized studies comparing long term clinical effectiveness is emphasized. [ABSTRACT FROM AUTHOR]

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Tuberculosis (TB) is a chronic bacterial disease, as well as a complex immune disease. The occurrence, development, and prognosis of TB are not only related to the pathogenicity of Mycobacterium tuberculosis (Mtb), but also related to the patient's own immune state. The research and development of immunotherapy drugs can effectively regulate the body's anti-TB immune responses, inhibit or eliminate Mtb, alleviate pathological damage, and facilitate rehabilitation. This paper reviews the research progress of immunotherapeutic compounds for TB, including immunoregulatory compounds and repurposing drugs, and points out the existing problems and future research directions, which lays the foundation for studying new agents for host-directed therapies of TB. [ABSTRACT FROM AUTHOR]

Background: Tick-borne diseases, caused by bacterial pathogens, pose a growing threat to public health in Europe. This paper provides an overview of the historical context of the discovery of the most impactful pathogens transmitted by ticks, including Borrelia burgdorferi sensu lato, Rickettsia spp., Anaplasma spp., Francisella spp., Ehrlichia spp., and Neoehrlichia mikurensis. Understanding the historical context of their discovery provides insight into the evolution of our understanding of these pathogens. Methods and results: Systematic investigation of the prevalence and transmission dynamics of these bacterial pathogens is provided, highlighting the intricate relationships among ticks, host organisms, and the environment. Epidemiology is explored, providing an in-depth analysis of clinical features associated with infections. Diagnostic methodologies undergo critical examination, with a spotlight on technological advancements that enhance detection capabilities. Additionally, the paper discusses available treatment options, addressing existing therapeutic strategies and considering future aspects. Conclusions: By integrating various pieces of information on these bacterial species, the paper aims to provide a comprehensive resource for researchers and healthcare professionals addressing the impact of bacterial tick-borne diseases in Europe. This review underscores the importance of understanding the complex details influencing bacterial prevalence and transmission dynamics to better combat these emerging public health threats. [ABSTRACT FROM AUTHOR]

The proliferation of drug-resistant bacteria and infections such as methicillin-resistant Staphylococcus aureus (MRSA) pose a serious challenge to global healthcare. Photothermal therapy (PTT) is becoming a highly effective antimicrobial method. Compared with near infrared I (NIR-I), near infrared II (NIR-II) has deeper penetration depth, less light scattering and higher maximum permissible exposure (MPE). The selection of a photothermal agent (PTA) and laser parameters is important. Three kinds of MXenes, Nb2C, Ti3C2 and V2C, were prepared in this paper, and the extinction coefficient and photothermal conversion efficiency (PCE) of NIR-I and NIR-II were compared. The extinction coefficient of Ti3C2 (26.23 L g−1 cm−1) at 808 nm was greater than those of Nb2C (24.38 L g−1 cm−1) and V2C (19.43 L g−1 cm−1). However, V2C had a higher temperature than Nb2C at 808 nm due to its high PCE (49.26%). Nb2C had a higher extinction coefficient (24.99 L g−1 cm−1) and PCE (45.55%) at 1064 nm, resulting in the highest temperature change. High extinction coefficient and high PCE are the two important factors for an excellent PTA. To reduce laser power used in the treatment, NIR-II laser and a gelation strategy for MXenes were used. The prepared Nb2C/Gel could be rapidly heated to 62 °C at a laser power of 0.112 W (lower than MPE), and the sterilization rate for MRSA was 92.48%. A NIH-3T3 cell activity study showed that the prepared Nb2C had good biocompatibility. Nb2C/Gel has excellent antibacterial properties and it is expected that a rapid, efficient and safe biological antimicrobial strategy against bacterial infections can be established using Nb2C/Gel, especially for drug-resistant bacterial infections. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic resistance threatens to make currently treatable bacterial diseases deadly again. As drug resistance rises, antibiotic susceptibility testing needs to adapt to allow for widespread, individualized testing. Paper-based diagnostics offer low-cost, disposable alternatives to traditional time consuming and costly in-house methods. Here, we describe a paper-based microfluidic device, called the Bac-PAC, capable of categorizing the antibiotic susceptibly of individual strains of Carbapenem-resistant Enterobacterales. Each chip provides a colored readout with actionable susceptibility classification of three antibiotics, thus maximizing the chances of identifying a viable therapy. We verified the technology on thirty bacterial strains with two dyes using six clinically relevant antibiotics. We demonstrated that the dried tests are stable for one month and can be incubated in a rechargeable coffee mug that reduces the need for external infrastructure. [ABSTRACT FROM AUTHOR]

The abuse of antibiotics urgently requires rapid identification of drug-resistant bacteria at the point of care (POC). Here we report a visual paper sensor that allows rapid (0.25-3 h) discrimination of the subtypes of β-lactamase (the major cause of bacterial resistance) for precision antibiotic therapy. The sensor exhibits high performance in identifying antibiotic-resistant bacteria with 100 real samples from patients with diverse bacterial infections, demonstrating 100% clinical sensitivity and specificity. Further, this sensor can enhance the accuracy of antibiotic use from 48% empirically to 83%, and further from 50.6% to 97.6% after eliminating fungal infection cases. Our work provides a POC testing platform for guiding effective management of bacterial infections in both hospital and community settings. The rapid identification of drug-resistant bacteria is vital for effective treatment and to avoid antibiotic misuse. Here authors report a paper-based sensor which utilises chromogenic carbapenem and cephalosporin substrates for the identification and discrimination of β-lactamase subtypes. [ABSTRACT FROM AUTHOR]

The specificity of phages and their ability to evolve and overcome bacterial resistance make them potentially useful as adjuncts in the treatment of antibiotic-resistant bacterial infections. The goal of this study was to mimic a natural grouping of phages of interest and to evaluate the nature of their proliferation dynamics with bacteria. We have, for the first time, transferred naturally occurring phage groups directly from their sources of isolation to in vitro and identified 13 P. aeruginosa and 11 K. pneumoniae phages of 18 different genera, whose host range was grouped as 1.2–17%, 28–48% and 60–87%, using a large collection of P. aeruginosa (n = 102) and K. pneumoniae (n = 155) strains carrying different virulence factors and phage binding receptors. We introduced the interpretation model curve for phage liquid culturing, which allows easy and quick analysis of bacterial and phage co-proliferation and growth of phage-resistant mutants (PRM) based on qualitative and partially quantitative evaluations. We assayed phage lytic activities both individually and in 14 different cocktails on planktonic bacterial cultures, including three resistotypes of P. aeruginosa (PAO1, PA14 and PA7) and seven K. pneumoniae strains of different capsular serotypes. Based on the results, the natural phage cocktails designed and tested in this study largely performed well and inhibited PRM growth either synergistically or in proto-cooperation. This study contributes to the knowledge of phage behavior in cocktails and the formulation of therapeutic phage preparations. The paper also provides a detailed description of the methods of working with phages. [ABSTRACT FROM AUTHOR]

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa—a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years—a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) have been one of the most common bacterial infections in clinical practice worldwide. Artificial intelligence (AI) and machine learning (ML) based algorithms have been increasingly applied in UTI case identification and prediction. However, the overall performance of AI/ML algorithms in identifying and predicting UTI has not been evaluated. The purpose of this paper is to quantitatively evaluate the application value of AI/ML in identifying and predicting UTI cases. Methods: MEDLINE, EMBASE, Web of Science, and PubMed databases were systematically searched for articles published up to December 31, 2023. Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) and Prediction Model Risk of Bias Assessment Tool (PROBAST) were used to assess the risk of bias. Study characteristics and detailed algorithm information were extracted. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were synthesized using a bivariate mix-effects model. Meta-regression and subgroup analysis were conducted to test the source of heterogeneity. Results: In total, 11 studies with 14 AI/ML models were included in the final meta-analysis. The overall pooled AUC was 0.89 (95%CI 0.86–0.92). Additionally, the pooled Sen, Spe, PLR, NLR, and DOR were 0.78 (95%CI 0.71–0.84), 0.89 (95%CI 0.83–0.93), 6.99 (95%CI 4.38–11.14), 0.25 (95%CI 0.18–0.34) and 28.07 (95%CI 14.27–55.20), respectively. The results of meta-regression suggested that reference standard definitions might be the source of heterogeneity. Conclusion: AI/ML algorithms appear to be promising to help clinicians detect and identify patients at high risk of UTIs. However, further studies are demanded to evaluate the application value of AI/ML more thoroughly. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is a significant global concern, necessitating the development of either new antibiotics or advanced delivery methods. With this in mind, we report on the synthesis and characterisation of a new family of Metal–Organic Frameworks (MOFs), OnG6 MOFs, designed to act as multi-drug carriers for bacterial infection treatment. OnG6 is based on the pro-drug 4,4′-azodisalicylic acid (AZDH4), which in vivo produces two equivalents of para-aminosalicylic acid (ASA), a crucial drug for M. tuberculosis treatment. X-ray and computational studies revealed that OnG6 MOFs are mesoporous MOFs with etb topology and an [M2(AZD)] formula (M = Zn, OnG6-Zn; Mg, OnG6-Mg; Cu, OnG6-Cu; and Co, OnG6-Co), featuring 1-dimensional channel type pores of 25 Å diameter. OnG6 MOFs are the first reported MOFs bearing the ligand AZDH4, joining the family of mesoporous MOFs arranged in a honeycomb pattern. They absorb isoniazid (INH) and ciprofloxacin (CIPRO) with the former being a specific antibiotic for M. tuberculosis, and the latter being a broader-spectrum antibiotic. The stability of the MOFs and their capacity for antibiotic uptake depend on the nature of the metal ion, with OnG6-Mg demonstrating the highest drug absorption. The antimicrobial activity of these species was assessed against S. aureus and E. coli, revealing that the carriers containing CIPRO displayed optimal efficacy. [ABSTRACT FROM AUTHOR]

Achilles tendon defect is caused by direct or indirect violence that makes it difficult for the tensile strength of the Achilles tendon to resist external forces. It is characterized by a lack of tissue integrity around the Achilles tendon, local bruising or bacterial infection, and ultimately leads to abnormal gait. This paper reviews the recent research progress of biodegradable polymeric materials in treating Achilles tendon defects at home and abroad, mainly introducing the therapeutic impact on the repair of Achilles tendon defects from materials alone, materials combined with drugs or cells. [ABSTRACT FROM AUTHOR]

Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations. [ABSTRACT FROM AUTHOR]

Introduction: Looking into the literature, many articles accuse bacterial persister cells as important causes of infection relapse/recalcitrance. This opinion paper, highlights the knowledge gaps and scientific misconceptions in experimental procedures regarding the role of persisters in relapse/recalcitrance of infections and recommends a roadmap for investigations in this field. Conclusion: It is debated in this paper, that unless the queries and missing points are addressed clearly, persisters cannot be stigmatized as the culprit of infection relapse/recalcitrance. [ABSTRACT FROM AUTHOR]

Background: Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately provide new information to shape public policy response on cholera control and elimination. Methodology/Principal findings: Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions: WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers this provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas. [ABSTRACT FROM AUTHOR]

The intrinsic hydrophilicity of conventional dressings cannot achieve effective management of excessive biofluid around the wound bed, which inevitably causes infection and hinders wound healing. In addition, present dressings such as medical gauze or band aids have a limited stretching capability, which does not comply well with the skin deformation during muscle movement, thus impacting patient comfort. Herein, a Janus wound dressing is reported by assembling an external hydrophobic (HP) adhesive tape, a filter paper, and a polydimethylsiloxane (PDMS) Janus film. The PDMS Janus film as the primary dressing can unidirectionally remove biofluid away from the wound bed. The mechanism of the unidirectional biofluid transport is investigated, demonstrating that the stretching or bending of the Janus dressing is beneficial for unidirectional biofluid draining. It indicates that the Janus PDMS film has potential for practical applications on stretched or bended skin surface. In addition, in order to prevent bacterial infection, amoxicillin powder is uniformly encapsulated on the HP layer of Janus film, resulting in faster wound healing. This study is valuable for designing and fabricating next‐generation dressings with high performance for clinical applications. [ABSTRACT FROM AUTHOR]

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g., tuberculosis and bacterial pneumonia), (2) bacterial infection is a consequence of disease and worsens the disease prognosis (e.g., cystic fibrosis), and (3) bacteria-triggered inflammation propagates the disease (e.g., chronic obstructive pulmonary disease). Current approaches to combat infections generally include long and aggressive antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of infections that cannot be treated with conventional antibiotics is rapidly increasing, and novel therapies are urgently needed. In this context, antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress inflammation and provide other host defense functions (motivating the alternative term host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this, AMP delivery systems have recently attracted attention. For airway infections, the currently investigated delivery approaches range from aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating bacterial infections in the airways. [ABSTRACT FROM AUTHOR]

Identifying and analyzing mixed pathogenic bacteria is important for clinical diagnosis and antibiotic therapy of multiple bacterial infection. In this paper, a dual-mode hyperspectral microscopic detection technology with hybrid deep neural networks (DNNs) was proposed for simultaneous quantitative analysis of four kinds of pathogenic bacteria in mixed samples. To acquire both transmission and fluorescence spectra regarding the mixed pathogens, we developed a dual-mode hyperspectral detection system with fine spectral resolution and wide wavelength range, which can also generate spatial images that can be used to calculate the total amount of mixed bacteria. The dual-mode spectra were regarded as mixed proportion characteristics and the input of the neural network for predicting the proportion of each bacterium present in the mixture. To better analyze the dual-mode spectral data, we customized a mixed bacteria measurement network (MB-Net) with hybrid DNNs architectures based on spectral feature fusion. Using the fusion strategy, two DNNs frameworks applied for transmission/fluorescence spectral feature processing were stacked to form the MB-Net that processes these features simultaneously, and the achieved average coefficient of determination (R2) and RMSE of validation set are 0.96 and 0.03, respectively. To the best of our knowledge, it is the first time of simultaneously detecting four types of mixed pathogenic bacteria using spectral detection technology, showing excellent potential in clinical practice. [ABSTRACT FROM AUTHOR]

Phages of phytopathogenic bacteria are considered to be promising agents for the biological control of bacterial diseases in plants. This paper reports on the isolation and characterisation of a new Xanthomonas campestris pv. campestris phage, Murka. Phage morphology and basic kinetic characteristics of the infection were determined, and a phylogenomic analysis was performed. The phage was able to lyse a reasonably broad range (64%, 9 of the 14 of the Xanthomonas campestris pv. campestris strains used in the study) of circulating strains of the cabbage black rot pathogen. This lytic myovirus has a DNA genome of 44,044 bp and contains 83 predicted genes. Taxonomically, it belongs to the genus Foxunavirus. This bacteriophage is promising for use as a possible means of biological control of cabbage black rot. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a bacterial infection that is well-known in the palaeopathological record because it can affect the skeleton and consequently leaves readily identifiable macroscopic alterations. Palaeopathological case studies provide invaluable information about the spatio-temporal distribution of TB in the past. This is true for those archaeological periods and geographical regions from when and where no or very few TB cases have been published until now–as in the Sarmatian period (1st–5th centuries CE) in the Barbaricum of the Carpathian Basin. The aim of our paper is to discuss five newly discovered TB cases (HK199, HK201, HK225, HK253, and HK309) from the Sarmatian-period archaeological site of Hódmezővásárhely–Kenyere-ér, Bereczki-tanya (Csongrád-Csanád county, Hungary). Detailed macromorphological evaluation of the skeletons focused on the detection of bony changes likely associated with different forms of TB. In all five cases, the presence of endocranial alterations (especially TB-specific granular impressions) suggests that these individuals suffered from TB meningitis. Furthermore, the skeletal lesions observed in the spine and both hip joints of HK225 indicate that this juvenile also had multifocal osteoarticular TB. Thanks to the discovery of HK199, HK201, HK225, HK253, and HK309, the number of TB cases known from the Sarmatian-period Carpathian Basin doubled, implying that the disease was likely more frequent in the Barbaricum than previously thought. Without the application of granular impressions, the diagnosis of TB could not have been established in these five cases. Thus, the identification of TB in these individuals highlights the importance of diagnostics development, especially the refinement of diagnostic criteria. Based on the above, the systematic macromorphological (re-)evaluation of osteoarchaeological series from the Sarmatian-period Carpathian Basin would be advantageous to provide a more accurate picture of how TB may have impacted the ancestral human communities of the Barbaricum. [ABSTRACT FROM AUTHOR]

Diphtheria is a fatal bacterial infection primarily affecting the respiratory system, characterized by a thick membrane formation in the throat, caused by Corynebacterium diphtheriae. This manuscript elucidates sociological interventions, aimed at protecting the population of Nigeria from diphtheria, a preventable yet persisting health threat. It delves into diverse strategies that could be employed to combat misconceptions, navigate deeply ingrained cultural biases, and instill the significance of vaccination within the context of diphtheria outbreak and prevention. The research question was: "What are the sociological interventions, used to address misconceptions, cultural biases, and promote vaccination in the context of diphtheria prevention in Nigeria?" In response to this inquiry, a comprehensive review methodology was employed to systematically gather, evaluate, and synthesize relevant literature outputs. The literature search, conducted across diverse academic databases and repositories, yields a rich collection of studies, reports, and case studies. The lens of Symbolic Interactionism was applied. The sociological interventions, considered in this context, engage directly with communities, healthcare providers, and local leaders. It addresses the vital need to combat misconceptions, cultural biases, and vaccine hesitancy, fostering a deeper understanding of the dynamic interplay between sociological factors and healthcare interventions. Sociological interventions for diphtheria protection in Nigeria require culturally sensitive approaches, community engagement, health education, addressing vaccine hesitancy, offering accessible vaccination services, tackling socioeconomic barriers, targeted messaging, behavioral change communication, data collection, and research collaborations to understand and address sociocultural factors influencing vaccine uptake and prevention. The findings and implications offer valuable insights for policymakers, healthcare providers, and researchers, and lay the groundwork for more effective strategies to protect the population from this preventable disease. [ABSTRACT FROM AUTHOR]

Striped catfish, Pangasianodon hypophthalmus is a native species to most Asian countries, including Malaysia which faced series of bacterial disease such as edwardsiellosis caused by E.ictaluri. Edwardsiella ictaluri is a Gram-negative intracellular bacterial pathogen which had caused mortalities in farmed or wild fish in lots of countries and accountable for large economic losses. This study was conducted to determine disease status of Pangasius spp due to Edwardsiella ictaluri and to determine the risk factors of E.ictaluri in striped catfish in Pahang River, Malaysia. Four sampling sites were chosen, two sites in Pekan (Kampung Belimbing and Kampung Tanjung Pulai) and two sites in Temerloh (Kampung Teluk Ira and Kampung Bintang). Thirty samples were collected from each farm for 6 months consecutively and four organ tissues were taken which were liver, spleen, kidney, and brain. External and internal clinical signs were recorded accordingly. DNA was extracted from all tissues and pursued for PCR to detect the presence of Edwardsiella ictaluri. Results show that the infected fish has gross internal clinical signs such as patchy liver, white nodular spleen, and congested kidney. The prevalence rate of E.ictaluri was highest at Kampung Tanjung Pulai in June with 16.67% compared to all farms. No infection of E.ictaluri shown at Kampung Belimbing during the whole sampling session. Spearman's rho correlation showed that the prevalence of E.ictaluri has strong correlation with temperature in Kampung Tanjung Pulai (p > 0.05). Meanwhile those bacteria prevalence have strong relationship with ammonia, sulfide and total suspended solid (TSS) with p< 0.05. The susceptible size for this bacterium in striped catfish is between 1 to 50g. To our knowledge, this paper is the first report for Edwardsiella ictaluri in cage cultured P.hypopthalmus in Pahang River, Malaysia. [ABSTRACT FROM AUTHOR]

Although Streptococcus pneumoniae has been one of the most common bacterial causes of disease in humans, its impact has been blunted by the broad use of vaccines. Since 2018, the incidence of invasive pneumococcal disease in Korea decreased with effective pneumococcal vaccines but is on the rise again recently. In this paper I will review the epidemiology, risk factors, and antibiotic resistance of invasive pneumococcal disease after the introduction of the pneumococcal vaccine in Korean adults. [ABSTRACT FROM AUTHOR]

Nowadays there is a growing interest worldwide in using bacteriophages for therapeutic purposes to combat antibiotic-resistant bacterial strains, driven by the increasing ineffectiveness of drugs against bacterial infections. Despite this fact, no novel commercially available therapeutic phage products have been developed in the last two decades, as it is extremely difficult to register them under the current legal regulations. This paper presents a description of the interaction between a bacteriophage manufacturer and a clinical institution, the specificity of which is the selection of bacteriophages not for an individual patient, but for the entire spectrum of bacteria circulating in the intensive care unit with continuous clinical and microbiological monitoring of efficacy. The study presents the description of three clinical cases of patients who received bacteriophage complex via inhalation for 28 days according to the protocol without antibiotic use throughout the period. No adverse effects were observed and the elimination of multidrug-resistant microorganisms from the bronchoalveolar lavage contents was detected in all patients. A decrease in such inflammatory markers as C-reactive protein (CRP) and procalcitonin was also noted. The obtained results demonstrate the potential of an adaptive phage therapy protocol in intensive care units for reducing the amount of antibiotics used and preserving their efficacy. [ABSTRACT FROM AUTHOR]

This paper reviews different approaches to obtain biomaterials with tailored functionalities and explains their significant characteristics that influence their bioactivity. The main goal of this discussion underscores the significance of surface properties in materials, with a particular emphasis on their role in facilitating cell adhesion in order to obtain good biocompatibility and biointegration, while preventing adverse effects, such as bacterial contamination and inflammation processes. Consequently, it is essential to design strategies and interventions that avoid bacterial infections, reducing inflammation and enhancing compatibility systems. Within this review, we elucidate the most prevalent techniques employed for surface modification, notably emphasizing surface chemical composition and coatings. In the case of surface chemical composition, we delve into four commonly applied approaches: hydrolysis, aminolysis, oxidation, and plasma treatment. On the other hand, coatings can be categorized based on their material composition, encompassing ceramic-based and polymer-based coatings. Both types of coatings have demonstrated efficacy in preventing bacterial contamination, promoting cell adhesion and improving biological properties of the surface. Furthermore, the addition of biological agents such as drugs, proteins, peptides, metallic ions plays a pivotal role in manifesting the prevention of bacterial infection, inflammatory responses, and coagulation mechanism. [ABSTRACT FROM AUTHOR]

The constant presence of infectious diseases poses an everlasting threat to the entire world. In recent years, there has been an increased attention toward the application of traditional Chinese medicine (TCM) in the treatment of emerging infectious diseases, as it has played a significant role. The aim of this article is to provide a concise overview of the roles and mechanisms of TCM in treating infectious diseases. TCM possesses the ability to modulate relevant factors, impede signaling pathways, and inhibit microbial growth, thereby exhibiting potent antiviral, antibacterial, and anti-inflammatory effects that demonstrate remarkable efficacy against viral and bacterial infections. This article concludes that the comprehensive regulatory features of Chinese herbal medicines, with their various components, targets, and pathways, result in synergistic effects. The significance of Chinese herbal medicines in the context of infectious diseases should not be underestimated; however, it is crucial to also acknowledge their underutilization. This paper presents constructive suggestions regarding the challenges and opportunities faced by Chinese medicines. Particularly, it emphasizes the effectiveness and characteristics of Chinese medicines in the treatment of infectious diseases, specifying how these medicines’ active substances can be utilized to target infectious diseases. This perspective is advantageous in facilitating researchers’ pharmacological studies on Chinese medicines, focusing on the specific points of action. The mechanism of action of Chinese herbal medicines in the treatment of infectious diseases is comprehensively elucidated in this paper, providing compelling evidence for the superior treatment of infectious diseases through Chinese medicine. This information is favorable for advancing the development of TCM and its potential applications in the field of infectious diseases. [ABSTRACT FROM AUTHOR]

Bacterial infections are a leading cause of death globally. The detection of DNA sequences correlated to the causative pathogen has become a vital tool in medical diagnostics. In practice, PCR-based assays for the simultaneous detection of multiple pathogens currently rely on probe-based quantitative strategies that require expensive equipment but have limited sensitivity or multiplexing capabilities. Hence, novel approaches to address the limitations of the current gold standard methods are still in high demand. In this study, we propose a simple multiplex PCR/SERS assay for the simultaneous detection of four bacterial pathogens, namely P. aeruginosa, S. aureus, S. epidermidis, and M. smegmatis. Wherein, specific primers for amplifying each target gDNA were applied, followed by applying SERS nanotags functionalized with complementary DNA probes and Raman reporters for specific identification of the target bacterial pathogens. The PCR/SERS assay showed high specificity and sensitivity for genotyping bacterial pathogen gDNA, whereby as few as 100 copies of the target gDNA could be detected. With high sensitivity and the convenience of standard PCR amplification, the proposed assay shows great potential for the sensitive detection of multiple pathogen infections to aid clinical decision-making. [ABSTRACT FROM AUTHOR]

Bacterial infections are a leading cause of death globally. The detection of DNA sequences correlated to the causative pathogen has become a vital tool in medical diagnostics. In practice, PCR-based assays for the simultaneous detection of multiple pathogens currently rely on probe-based quantitative strategies that require expensive equipment but have limited sensitivity or multiplexing capabilities. Hence, novel approaches to address the limitations of the current gold standard methods are still in high demand. In this study, we propose a simple multiplex PCR/SERS assay for the simultaneous detection of four bacterial pathogens, namely P. aeruginosa, S. aureus, S. epidermidis, and M. smegmatis. Wherein, specific primers for amplifying each target gDNA were applied, followed by applying SERS nanotags functionalized with complementary DNA probes and Raman reporters for specific identification of the target bacterial pathogens. The PCR/SERS assay showed high specificity and sensitivity for genotyping bacterial pathogen gDNA, whereby as few as 100 copies of the target gDNA could be detected. With high sensitivity and the convenience of standard PCR amplification, the proposed assay shows great potential for the sensitive detection of multiple pathogen infections to aid clinical decision-making. [ABSTRACT FROM AUTHOR]

Veterinarians are at risk for numerous zoonotic infections. In this paper, we summarise descriptions of zoonotic infections from a questionnaire study and a series of work-related zoonotic cases, aiming to add to the knowledge on occupational zoonotic risks of veterinarians. We collected data on zoonotic infections contracted by veterinarians in Finland in two studies:1) using a questionnaire in 2009, and 2) inviting veterinarians who had encountered an occupational zoonosis to report it in structured interviews in 2019. In the questionnaire study in 2009, of 306 veterinarians several reported zoonotic bacterial skin infections (12%), dermatophytosis (ringworm; 4.2%), virus infections (3.9%), bacterial gastroenteritis (3.3%), other bacterial zoonoses (2.3%), and parasitic infections/infestations (2.3%). In the 2019 interviews, 16 occupational zoonosis cases were reported. Of them, seven were selected to the case series. The selected cases included Capnocytophaga canimorsus sepsis following a dog bite, cryptosporidiosis after a contact with calves, cutaneous listeriosis following calving assistance, Salmonella gastroenteritis contracted at laboratory, Trichophyton dermatophytosis after equine contact, Bacillus anthracis exposure at necropsy, and exposure to rabies through a horse bite. In four of the seven cases, the veterinarian disagreed or strongly disagreed with having had good knowledge of the zoonosis before the incident. The results from the questionnaire study and the case series illustrate the variety of zoonotic pathogens that veterinarians may encounter. There is a need to improve the occupational health of veterinarians and to increase awareness in the occupational health sector. We encourage addressing this need using a One Health approach. [ABSTRACT FROM AUTHOR]

Objective This paper presents a rare case of subacute bacterial endocarditis (SBE) following a herpes zoster (HZ) episode, with no prior records found in the existing literature. Patient information Specifically, we describe a case of a 76-year-old female whose diagnosis of SBE was hindered by the concurrent manifestation of HZ symptoms, which had emerged 3 weeks before the onset of SBE indicators. Follow-up and outcomes This delay in diagnosis resulted in profound complications, including a cerebrovascular accident and significant mitral valve destruction. Discussion HZ episodes have not conventionally been linked in the medical literature to the occurrence of SBE. Nonetheless, it is noteworthy that HZ infections have been associated with the development of other consequential bacterial infections, such as pneumonia and necrotizing fasciitis. This case underscores the necessity for medical practitioners to recognize the possibility of HZ symptoms obscuring indications of critical underlying conditions and infections. The implications of this report highlight the significance of maintaining heightened vigilance for signs of other severe infections when managing patients presenting with HZ symptoms. [ABSTRACT FROM AUTHOR]

Silver nanoparticles have shown inhibitory capabilities and its use in battling viral infections are strengthened by its potent antibacterial activity. Notably, since it directly affects antiviral efficacy, the proper choice of synthesis process for making silver nanoparticles is a vital element to be taken into consideration. The synthesis of silver nanoparticles for the treatment of viral and bacterial infections involves creating silver particles at the nanoscale with unique antimicrobial properties. Various methods exist for synthesizing silver nanoparticles, including chemical reduction, green synthesis, and physical methods. Chemical reduction involves using reducing agents to convert silver ions into silver nanoparticles. Green synthesis employs reducing agents in an environmentally friendly manner. Physical methods rely on techniques such as laser ablation or thermal evaporation to produce silver nanoparticles. In order to provide technological guidance for choosing antiviral silver nanoparticle manufacturing methods, this paper introduces and explores alternative synthesis methods for creating silver nanoparticles. [ABSTRACT FROM AUTHOR]

In countries like India, diseases in plants are a major concern in the agricultural sector. Crop loss due to diseases led to reduction in the quality and quantity of agricultural products. This also leads to economic losses. Hence, timely monitoring of plants is necessary. But monitoring diseases in large fields is a difficult task. To overcome this problem, effective management strategies should be taken to control diseases in plants. It can be done by acquiring data for disease identification and automation of the recognition of diseases. Deep learning is of great use in this area using the principles of object detection. In this paper, we are using YOLOv3 (you only look once) to determine the diseases in plants, based on the symptoms seen on the leaves. The advantage of using YOLOv3 is that multiple diseases can be detected on the image of a single leaf. An important feature of YOLOv3 is that it can detect small disease spots seen on the leaves. Here, we are concentrating on the bacterial spot disease seen on the bell pepper plant. The identification results show a mean average precision of 90%. [ABSTRACT FROM AUTHOR]

Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage–bacteria relationships. In this paper, we present, PB-LKS, to predict the phage–bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant bacteria have proliferated at an alarming rate as a result of the extensive use of antibiotics and the paucity of new medication research. The possibility that an antibiotic-resistant bacterial infection would progress to sepsis is one of the major collateral problems affecting people with this condition. 31,000 lives were lost due to sepsis in England with costs about two billion pounds annually. This research aims to develop and evaluate several classification approaches to improve predicting sepsis and reduce the tendency of underdiagnosis in computer-aided predictive tools. This research employs medical datasets for patients diagnosed with sepsis, and it analyses the efficacy of ensemble machine learning techniques compared to nonensemble machine learning techniques and the significance of data balancing and conditional tabular generative adversarial nets for data augmentation in producing reliable diagnosis. The average F Score obtained by the nonensemble models trained in this paper is 0.83 compared to the ensemble techniques average of 0.94. Nonensemble techniques, such as Decision Tree, achieved an F score of 0.90, an AUC of 0.90, and an accuracy of 90%. Histogram-basedgradient boosting classification tree achieved an F score of 0.96, an AUC of 0.96, and an accuracy of 95%, surpassing the other models tested. Additionally, when compared to the current state-of-the-art sepsis prediction models, the models developed in this study demonstrated higher average performance in all metrics, indicating reduced bias and improved robustness through data balancing and conditional tabular generative adversarial nets for data augmentation. The study revealed that data balancing and augmentation on the ensemble machine learning algorithms boost the efficacy of clinical predictive models and can help clinics decide which data types are most important when examining patients and diagnosing sepsis early through intelligent human-machine interface. [ABSTRACT FROM AUTHOR]

Glycans on the surface of bacteria have diverse and essential biological functions and have widely been employed for treating various bacterial infectious diseases. Furthermore, these glycans comprise various functional groups, such as O-, N-, and carboxyl-modified, which significantly increase the diversity of glycan structures. These functional groups are not only crucial for glycans' structural identity but are also essential for their biological functions. Therefore, a clear understanding of the biological functions of these modified groups in corresponding bacterial glycans is crucial for their medical applications. Thus far, the activities of functional groups in some biomedical active carbohydrates have been elucidated. It has been shown that some functional groups are key constituents of biologically active bacterial glycans, while others are actually not essential and may even mask the functions of the glycans. This paper reviews the structures of naturally occurring side-chain functional groups in glycans located on the bacterial surface and their roles in immunological responses. [ABSTRACT FROM AUTHOR]

Cotton is one of the most important agricultural products and is closely linked to the economic development of Pakistan. However, the cotton plant is susceptible to bacterial and viral diseases that can quickly spread and damage plants and ultimately affect the cotton yield. The automated and early detection of affected plants can significantly reduce the potential spread of the disease. This paper presents the implementation and performance analysis of bacterial blight and curl virus disease detection in cotton crops through deep learning techniques. The automated disease detection is performed through transfer learning of six pre-trained deep learning models, namely DenseNet121, DenseNet169, MobileNetV2, ResNet50V2, VGG16, and VGG19. A total of 1362 images of local agricultural fields and 1292 images from online resources were used to train and validate the models. Image augmentation techniques were performed to increase the dataset diversity and size. Transfer learning was implemented for different image resolutions ranging from 32×32 to 256×256 pixels. Performance metrics such as accuracy, precision, recall, F1 Score, and prediction time were evaluated for each implemented model. The results indicate higher accuracy, up to 96%, for DenseNet169 and ResNet50V2 models when trained on the 256×256 pixels image dataset. The lowest accuracy, 52%, was obtained by the MobileNetV2 model when trained on lowresolution, 32×32, images. The confusion matrix analysis indicates the true-positive prediction rates higher than 91% for fresh leaves, 87% for bacterial blight, and 76% for curl virus detection for all implemented models when trained and tested on an image dataset of 128×128 pixels or higher resolution. [ABSTRACT FROM AUTHOR]

Graphene, fullerenes, diamond, carbon nanotubes, and carbon dots are just a few of the carbon-based nanomaterials that have gained enormous popularity in a variety of scientific disciplines and industrial uses. As a two-dimensional material in the creation of therapeutic delivery systems for many illnesses, nanosized graphene oxide (NGO) is now garnering a large amount of attention among these materials. In addition to other benefits, NGO functions as a drug nanocarrier with remarkable biocompatibility, high pharmaceutical loading capacity, controlled drug release capability, biological imaging efficiency, multifunctional nanoplatform properties, and the power to increase the therapeutic efficacy of loaded agents. Thus, NGO is a perfect nanoplatform for the development of drug delivery systems (DDSs) to both detect and treat a variety of ailments. This review article's main focus is on investigating surface functionality, drug-loading methods, and drug release patterns designed particularly for smart delivery systems. The paper also examines the relevance of using NGOs to build DDSs and considers prospective uses in the treatment of diseases including cancer, infection by bacteria, and bone regeneration medicine. These factors cover the use of naturally occurring medicinal substances produced from plant-based sources. [ABSTRACT FROM AUTHOR]

This study included 72 participants with oral halitosis (35 men and 37 women), who had been clinically diagnosed and ranged in age from 14 to 70. 95 samples were obtained using sterile paper points (size 30) or sterile cotton swabs, in either aerobic or anaerobic conditions, thioglycolate broth was transported and blood agar was used for culture (for 48–72 hours). The bacteria were recognized by means of biochemical testing, tests for antibiotic susceptibility, and morphological and cultural features. Results revealed that 13 different bacterial species were isolated in this study, including Bacteriodes spp. (26 isolates), Viridans Streptococci (18 isolates), Peptostreptococci (19 isolates), Actinomyces spp. (15 isolates), Porphyromonas spp. (8 isolates), Fusobacterium spp. (9 isolates), Veillonella spp. (5 isolates), Streptococcus spp. (10 (2 isolates). The dominant anaerobic bacterial species and genera in instances of halitosis is the conclusion. [ABSTRACT FROM AUTHOR]

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Introduction: Paddy leaf diseases have a catastrophic influence on the quality and quantity of paddy grain production. The detection and identification of the intensity of various paddy infections are critical for high-quality crop production. Methods: In this paper, infections in paddy leaves are considered for the identification of illness severity. The dataset contains both primary and secondary data. The four online repositories used for secondary data resources are Mendeley, GitHub, Kaggle and UCI. The size of the dataset is 4,068 images. The dataset is first pre-processed using ImageDataGenerator. Then, a generative adversarial network (GAN) is used to increase the dataset size exponentially. The disease severity calculation for the infected leaf is performed using a number of segmentation methods. To determine paddy infection, a deep learning-based hybrid approach is proposed that combines the capabilities of a convolutional neural network (CNN) and support vector machine (SVM). The severity levels are determined with the assistance of a domain expert. Four degrees of disease severity (mild, moderate, severe, and profound) are considered. Results: Three infections are considered in the categorization of paddy leaf diseases: bacterial blight, blast, and leaf smut. The model predicted the paddy disease type and intensity with a 98.43% correctness rate. The loss rate is 41.25%. Discussion: The findings show that the proposed method is reliable and effective for identifying the four levels of severity of bacterial blight, blast, and leaf smut infections in paddy crops. The proposed model performed better than the existing CNN and SVM classification models. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a bacterial disease that remains a global health threat due to the millions of deaths attributed to it each year. The emergence of drug resistance has exacerbated and further increased the challenges in the fight against this illness. Despite the preventive measures using the application of the Bacillus Calmette-Guérin vaccine, the desired immunization outcome is not as high as expected. Conventional TB treatments exhibit serious limitations, such as adverse effects and prolonged duration, leading to a pressing need for alternative and more effective treatment options. Despite significant efforts, it took nearly four decades for diarylquinoline to become the most recently approved medicine for this disease. In addition, various possibilities, such as the usage of medications used for many other conditions (repurposed drugs), have been explored in order to speed up the process of achieving faster outcomes. Natural compounds derived from various sources (microorganisms, plants, and animals) have emerged as potential candidates for combating TB due to their chemical diversity and their unique modes of action. Finally, efforts towards the generation of novel vaccines have received considerable attention. The goal of this paper was to perform an analysis of the current state of treating drug-resistant TB and to evaluate possible approaches to this complicated challenge. Our focus is centered on highlighting new alternatives that can be used to combat resistant strains, which have potentiated the health crisis that TB represents. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in vancomycin-resistant E. faecalis. We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed type IV restriction inhibiting factor A (tifA), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages evolve to overcome antiphage defense systems. Using a CRISPR interference genetic approach, Bullen, Johnson, and colleagues discover a type IV restriction (TIV-RE) enzyme encoded on a mobilizable plasmid of multidrug resistant Enterococcus faecalis. This TIV-RE is a potent inhibitor of bacteriophage infection. [ABSTRACT FROM AUTHOR]

Background: Fungal periprosthetic joint infection (FPJI) is an infrequent but devastating complication that imposes a heavy burden on patients. At present, a consensus regarding the most optimal surgical option for patients with FPJI, the ideal duration of systemic antifungal treatment, and many other issues has not been reached. Methods: A comprehensive literature search was performed on the PubMed and Embase databases. The search criteria employed were as follows: (fungal OR candida OR mycotic) AND periprosthetic joint infection. Initially, the titles and abstracts were screened, and subsequently, studies deemed irrelevant or duplicative were eliminated. Following this, the complete texts of remaining articles were thoroughly examined. According to the inclusion and exclusion criteria, 489 joints in 24 articles were screened out. We further extracted the demographic characteristics (age, gender, body mass index, etc.), clinical presentation, fungal species, presence of bacterial coinfection, surgical methods, systemic and local antifungal therapy, and treatment outcomes. Subgroup data were analyzed according to fungal species and bacterial coinfection. Univariate logistic regression analysis was conducted to ascertain the risk factors associated with the infection recurrence. Results: A total of 506 fungi were identified within 489 joints. The most prevalent fungal species were Candida albicans (41.5%). Out of 247 joints (50.5%) presenting with concurrent fungal and bacterial infections. Among the initial surgical interventions, two-stage exchange was the most common (59.1%). The infection recurrence rates of DAIR, resection arthroplasty, two-stage, one-stage, and three-stage exchange were 81.4%, 53.1%, 47.7%, 35.0%, and 30%, respectively. The mean duration of systemic antifungal therapy was 12.8 weeks. The most common drugs used both in intravenous (55.9%) and oral therapy (84.0%) were fluconazole. The proportion of patients who used antifungal drugs after replantation (two-stage and three-stage) was 87.6%. 33.2% of cement spacer or fixed cement contained antifungal drugs, of which amphotericin B was the main choice (82.7%). FPJI caused by candida albicans (OR = 1.717, p = 0.041) and DAIR (OR = 8.433, p = 0.003) were risk factors for infection recurrence. Conclusions: Two-stage exchange remains the most commonly used surgical approach. The reliability of one- and three-exchange needs further evaluation due to the small sample size. Antifungal-loaded cement spacers, and direct intra-articular injections of antimycotics after reimplatation should be strongly considered. Medication is not standardized but rather individualized according to microbiology and the status of patients. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in vancomycin-resistant E. faecalis. We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed type IV restriction inhibiting factor A (tifA), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages evolve to overcome antiphage defense systems. Using a CRISPR interference genetic approach, Bullen, Johnson, and colleagues discover a type IV restriction (TIV-RE) enzyme encoded on a mobilizable plasmid of multidrug resistant Enterococcus faecalis. This TIV-RE is a potent inhibitor of bacteriophage infection. [ABSTRACT FROM AUTHOR]

The zebrafish Danio rerio has become a popular model host to explore disease pathology caused by infectious agents. A main advantage is its transparency at an early age, which enables live imaging of infection dynamics. While multispecies infections are common in patients, the zebrafish model is rarely used to study them, although the model would be ideal for investigating pathogen-pathogen and pathogen-host interactions. This may be due to the absence of an established multispecies infection protocol for a defined organ and the lack of suitable image analysis pipelines for automated image processing. To address these issues, we developed a protocol for establishing and tracking single and multispecies bacterial infections in the inner ear structure (otic vesicle) of the zebrafish by imaging. Subsequently, we generated an image analysis pipeline that involved deep learning for the automated segmentation of the otic vesicle, and scripts for quantifying pathogen frequencies through fluorescence intensity measures. We used Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, three of the difficult-to-treat ESKAPE pathogens, to show that our infection protocol and image analysis pipeline work both for single pathogens and pairwise pathogen combinations. Thus, our protocols provide a comprehensive toolbox for studying single and multispecies infections in real-time in zebrafish. [ABSTRACT FROM AUTHOR]

Live vaccines are ideal for inducing immunity but suffer from the need to attenuate their pathogenicity or replication to preclude the possibility of escape. Unnatural amino acids (UAAs) provide a strategy to engineer stringent auxotrophies, yielding conditionally replication incompetent live bacteria with excellent safety profiles. Here, we engineer Pseudomonas aeruginosa to maintain auxotrophy for the UAA p-benzoyl-l-phenylalanine (BzF) through its incorporation into the essential protein DnaN. In vivo evolution using an Escherichia coli-based two-hybrid selection system enabled engineering of a mutant DnaN homodimeric interface completely dependent on a BzF-specific interaction. This engineered strain, Pa Vaccine, exhibits undetectable escape frequency (<10−11) and shows excellent safety in naïve mice. Animals vaccinated via intranasal or intraperitoneal routes are protected from lethal challenge with pathogenic P. aeruginosa PA14. These results establish UAA-auxotrophic bacteria as promising candidates for bacterial vaccine therapy and outline a platform for expanding this technology to diverse bacterial pathogens. In this work, authors develop a live vaccine candidate against Pseudomonas aeruginosa using an unnatural amino acid-based auxotrophic strategy. They provide insight on the vaccine's in vivo safety profile and protection of mice against lethal P. aeruginosa challenge. [ABSTRACT FROM AUTHOR]

Understanding the dynamic evolution of Salmonella is vital for effective bacterial infection management. This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of Salmonella lineages. Through comprehensive genomic analysis of 12,244 Salmonella spp. genomes covering 2 species, 6 subspecies, and 46 serovars, we uncover distinct integration patterns of pathogenicity-related gene clusters into RGP, challenging traditional views of gene distribution. These RGP exhibit distinct preferences for specific genomic spots, and the presence or absence of such spots across Salmonella lineages profoundly shapes strain pathogenicity. RGP preferences are guided by conserved flanking genes surrounding integration spots, implicating their involvement in regulatory networks and functional synergies with integrated gene clusters. Additionally, we emphasise the multifaceted contributions of plasmids and prophages to the pathogenicity of diverse Salmonella lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of Salmonella. This unique insight identifies genomic spots in nonpathogenic lineages that hold the potential for harbouring pathogenicity genes, providing a foundation for predicting future adaptations and developing targeted strategies against emerging human pathogenic strains. Effective management of Salmonella infections requires understanding its dynamic evolution. This study shows how specific genomic regions influence the distribution of pathogenicity factors in Salmonella, highlighting the potential for targeted infection control strategies. [ABSTRACT FROM AUTHOR]